PATHOLOGY AND DIAGNOSTICS
Beyond diagnosis
and classification:
‘the tissue is the issue’
In oncology immunotherapy, as in targeted therapy, the era of ‘one size fits all’
is past and the day-to-day work of pathologists is changing dramatically
Massimo Barberis MD
Elena Guerini-Rocco MD
Clinic Unit of
Histopathology and
Molecular Diagnostics,
Istituto Europeo di
Oncologia, Milan, Italy
Reference
1Kalemkerian G et al. Molecular
testing guideline for the
selection of patients with
lung cancer for treatment
with targeted tyrosine kinase
inhibitors: American Society of
Clinical Oncology Endorsement
of the College of American
Pathologists/International
Association for the Study of Lung
Cancer/Association for Molecular
Pathology Clinical Practice
Guideline Update. J Clin Oncol
2018;36:911–19.
Many hospitals with active oncology departments
require access to pathology laboratories to enable
a complete molecular profile of a tumour from
relevant biopsies. At the same time, new drugs for
targeted therapy and immunotherapy are
becoming available and many of them are used in
combination or sequentially to avoid resistance
mechanisms. However, a consequence of this
revolution in cancer treatment is that a new
challenge is looming on the horizon for the
pathologists: that is, to work beyond the diagnosis
and classification and directly contribute to
optimising rapid patient treatment with
sustainable costs.
The choice of analytical methods depends on
clinical requirements, availability of space,
expertise of the staff and dedicated budget. In our
Unit, we chose a multimarker-approach based on
next generation sequencing (NGS) platforms (for
example, ThermoFisher Scientific). Serial testing
takes time and depletes tumour tissue and the
cost of single-gene methods scales linearly with
the number of interrogated genes, which led us to
choose our current approach. The ASCO
endorsement of the College of American
Pathologists/International Association for the
Study of Lung Cancer/Association for Molecular
Pathology Clinical Practice Guideline Update 1
stated that multiplexed panels are likely to be
more efficient in terms of cost and tissue
requirements than other technologies.
Currently we receive 4000 requests of
molecular tests per year mainly for advanced
solid tumours (non-small cell lung cancer
(NSCLC), colorectal carcinomas and malignant
melanomas represent 80% of the samples).
A panel of 22 genes (Oncomine Dx Solid Tumors)
is offered to all the patients, whereas more
complex panels (Oncomine Focus and Oncomine
Comprehensive Assays) identifying not only
mutations but also copy number variations,
and fusion genes can be used in selected cases
(Table 1).
Immunotherapy is transforming oncology and
its use in many solid tumours and Hodgkin’s
lymphoma has become a stronghold in the
changing landscape of cancer treatment. Immune
checkpoint inhibition is exemplified by the
TABLE 1
Example of targeted next generation sequencing in NSCLC
Assay
Company
Gene# Technologies
Data Clinical Clinical Fee
routine
trial
paying
pz
CE-IVD Oncomine
Solid Tumor DNA
Custom DNA
panel
ThermoFisher
22
Scientific Ion
AmpliSeq SNVs,
Indels X
ThermoFisher
26
Scientific Ion
SNVs,
AmpliSeq Indels X
ThermoFisher 52 Ion SNVs,
X X X
Oncomine Focus
Scientific
AmpliSeq
Indels, CNGs
Asssay
Fusiongenes
Oncomine ThermoFisher
143/161
Ion X
Comprehensive Scientific AmpliSeq
Assay v1/v3
Foundation 324
Hybrid-
SNVs, X
FoundationOne
Medicine
capture
Indels, CNVs
Roche Fusiongenes
TMB+MSI
14
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